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Cancers
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Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management
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Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 6195

Special Issue Editor

Dr. Juan Manuel Rosa-Rosa

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Guest Editor
Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain
Interests: hematologic malignancies; multiple myeloma; next generation sequencing; molecular heterogeneity

Special Issue Information

Dear Colleagues,

Many studies have demonstrated multiple myeloma (MM) to be a complex and heterogeneous disease, with an expansion of genetic events that impact the prognosis of patients. Currently, next-generation sequencing allows for the understanding and classification of the genomic landscape of MM, in which the presence of “high-risk” features keeps predicting poorer outcomes, regardless of the effectiveness of novel treatments. Thus, multiple myeloma is still considered incurable, although recent clinical trials have shown promising results in regard to the stabilization of the disease, furthering the five-year threshold. However, there still remain many features requiring consideration, with the rise in improved disease monitorization through the use of the minimal residual disease analysis and its association with relapse probability.

Inviting contributions: This Special Issue welcomes research articles and review papers focused on a wide scope of multiple myeloma, from basic pathology to preclinical and clinical studies.

Dr. Juan Manuel Rosa-Rosa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple myeloma (MM)
  • hematologic malignancies
  • next-generation sequencing
  • heterogeneous disease
  • tumor heterogeneity
  • genomic landscape
  • outcomes
  • novel treatments
  • clinical trial

Published Papers (4 papers)

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15 pages, 3922 KiB  
Article
A Fully Human IgE Specific for CD38 as a Potential Therapy for Multiple Myeloma
by Pierre V. Candelaria, Miguel Nava, Tracy R. Daniels-Wells and Manuel L. Penichet
Cancers 2023, 15(18), 4533; https://doi.org/10.3390/cancers15184533 - 13 Sep 2023
Viewed by 1059
Abstract
Multiple myeloma (MM) is an incurable malignancy of plasma cells and the second most common hematologic malignancy in the United States. Although antibodies in clinical cancer therapy are generally of the IgG class, antibodies of the IgE class have attractive properties as cancer [...] Read more.
Multiple myeloma (MM) is an incurable malignancy of plasma cells and the second most common hematologic malignancy in the United States. Although antibodies in clinical cancer therapy are generally of the IgG class, antibodies of the IgE class have attractive properties as cancer therapeutics, such as their high affinity for Fc receptors (FcεRs), the low serum levels of endogenous IgE allowing for less competition for FcR occupancy, and the lack of inhibitory FcRs. Importantly, the FcεRs are expressed on immune cells that elicit antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and/or antigen presentation such as mast cells, eosinophils, macrophages, and dendritic cells. We now report the development of a fully human IgE targeting human CD38 as a potential MM therapy. We targeted CD38 given its high and uniform expression on MM cells. The novel anti-CD38 IgE, expressed in mammalian cells, is properly assembled and secreted, exhibits the correct molecular weight, binds antigen and the high affinity FcεRI, and induces degranulation of FcεRI expressing cells in vitro and also in vivo in transgenic BALB/c mice expressing human FcεRIα. Moreover, the anti-CD38 IgE induces ADCC and ADCP mediated by monocytes/macrophages against human MM cells (MM.1S). Importantly, the anti-CD38 IgE also prolongs survival in a preclinical disseminated xenograft mouse model using SCID-Beige mice and human MM.1S cells when administered with human peripheral blood mononuclear cells (PBMCs) as a source of monocyte effector cells. Our results suggest that anti-CD38 IgE may be effective in humans bearing MM and other malignancies expressing CD38. Full article
(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)
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15 pages, 1345 KiB  
Article
Thiazolidinedione Use Is Associated with a Borderline Lower Risk of Multiple Myeloma and a Significantly Lower Risk of Death in Patients with Type 2 Diabetes Mellitus in Taiwan
by Chin-Hsiao Tseng
Cancers 2023, 15(17), 4276; https://doi.org/10.3390/cancers15174276 - 26 Aug 2023
Viewed by 871
Abstract
Background: Thiazolidinedione (TZD) exerts anti-proliferative effects on multiple myeloma (MM) cells. However, there has not been any human study investigating the risk of MM associated with TZD use. Methods: We used Taiwan’s National Health Insurance database to identify 423,949 patients who had been [...] Read more.
Background: Thiazolidinedione (TZD) exerts anti-proliferative effects on multiple myeloma (MM) cells. However, there has not been any human study investigating the risk of MM associated with TZD use. Methods: We used Taiwan’s National Health Insurance database to identify 423,949 patients who had been newly diagnosed with diabetes mellitus between 1999 and 2005. After excluding ineligible patients, 86,999 pairs of patients with and without the use of TZD (rosiglitazone or pioglitazone) that had been matched based on propensity score were selected for a follow-up for MM until 31 December 2011. The hazard ratios for MM were estimated using Cox regression and weighted using a propensity score. Results: After a median follow-up of 4.6 years and 4.7 years in ever users and never users of TZD, 32 and 47 cases were diagnosed with MM, respectively. A 35% lower risk (though not statistically significant) was observed among ever users (hazard ratio 0.652, 95% confidence interval: 0.416–1.023, p = 0.0625). When ever users were divided by the median (15 months) cumulative duration of TZD therapy, the hazard ratios (95% confidence interval) for the lower and upper medians were 0.706 (0.394–1.264) and 0.603 (0.346–1.051), respectively. When treated as a continuous variable, the hazard ratio for every 1-month increment of the cumulative duration was 0.980 (95% confidence interval: 0.963–0.997, p = 0.0185). In the age subgroup analysis, a significantly lower risk could be seen in the older age subgroup of ≥65 years (hazard ratio 0.550, 95% confidence interval: 0.305–0.992, p = 0.0468). Additional analyses suggested that there were no interactions between TZD and some medications and between TZD and some clinical diagnoses, and that the use of TZD as a preventive drug for MM might not be cost-effective because a number-needed-to-treat of 5800 was too large. Survival analyses suggested that ever users had a significantly lower risk of death when all patients were analyzed (hazard ratio: 0.84, 95% confidence interval: 0.81–0.87, p < 0.0001 via a log-rank test) or when patients who developed MM were analyzed (hazard ratio: 0.40, 95% confidence interval: 0.19–0.86, p = 0.0153 via a log-rank test). Conclusions: In Taiwanese patients with type 2 diabetes mellitus, TZD use is associated with a borderline lower risk of MM, which is more remarkable in patients aged ≥65 years. Because of the low incidence of MM, the use of TZD for the prevention of MM may not be cost-effective. Patients who have been treated with TZD may have a survival advantage. Future research is required to confirm the findings. Full article
(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)
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14 pages, 1581 KiB  
Article
Lenalidomide Maintenance and Measurable Residual Disease in a Real-World Multiple Myeloma Transplanted Population Receiving Different Treatment Strategies Guided by Access to Novel Drugs in Brazil
by Anna Beatriz dos Santos Salgado, Roberto Jose Pessoa Magalhães, Robéria M. Pontes, Eduarda da Silva Barbosa, Juan Flores-Montero, Luzalba Sanoja-Flores, Marcelo Gerardin Poirot Land, Glicinia Pimenta, Hélio dos Santos Dutra, Elaine S. Costa, Alberto Orfao and Angelo Maiolino
Cancers 2023, 15(5), 1605; https://doi.org/10.3390/cancers15051605 - 04 Mar 2023
Viewed by 1939
Abstract
Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has [...] Read more.
Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has refined the prognosis of complete response (CR) cases, until now, there have been no data on the benefits of these approaches in Latin America. Here, we evaluate the benefits of M-Len and MRD using next-generation flow cytometry (NGF-MRD) at Day + 100 post-ASCT (n = 53). After ASCT, responses were evaluated based on the International Myeloma Working Group criteria and NGF-MRD. MRD was positive in 60% of patients with a median progression-free survival (PFS) of 31 months vs. not reached (NR) for MRD-negative cases (p = 0.05). The patients who received M-Len continuously had a significantly better PFS and overall survival (OS) than those without M-Len (median PFS: NR vs. 29 months, p = 0.007), with progression in 11% vs. 54% of cases after a median follow-up of 34 months, respectively. In a multivariate analysis, MRD status and M-Len therapy emerged as independent predictors of PFS (median PFS of M-Len/MRD− vs. no M-Len/MRD+ of NR vs. 35 months, respectively; p = 0.01). In summary, M-Len was associated with improved survival outcomes in our real-world MM cohort in Brazil, with MRD emerging as a useful reproducible tool to identify patients at an earlier risk of relapse. The inequity in drug access remains a hurdle in countries with financial constraints, with a negative impact on MM survival. Full article
(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)
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11 pages, 945 KiB  
Perspective
Identification of Immunoglobulin Gene Rearrangement Biomarkers in Multiple Myeloma through cfDNA-Based Liquid Biopsy Using tchDNA-Seq
by Natalia Buenache, Andrea Sánchez-delaCruz, Isabel Cuenca, Alicia Giménez, Laura Moreno, Joaquín Martínez-López and Juan Manuel Rosa-Rosa
Cancers 2023, 15(11), 2911; https://doi.org/10.3390/cancers15112911 - 25 May 2023
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Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response [...] Read more.
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response ultimately relapse. The earlier detection of tumor-related clonal DNA would thus be very beneficial for patients with MM and would enable timely therapeutic interventions to improve outcomes. Liquid biopsy of “cell-free DNA” (cfDNA) as a minimally invasive approach might be more effective than BM aspiration not only for the diagnosis but also for the detection of early recurrence. Most studies thus far have addressed the comparative quantification of patient-specific biomarkers in cfDNA with PPCs and BM samples, which have shown good correlations. However, there are limitations to this approach, such as the difficulty in obtaining enough circulating free tumor DNA to achieve sufficient sensitivity for the assessment of minimal residual disease. Herein, we summarize current data on methodologies to characterize MM, and we present evidence that targeted capture hybridization DNA sequencing (tchDNA-Seq) can provide robust biomarkers in cfDNA, including immunoglobulin (IG) rearrangements. We also show that detection can be improved by prior purification of the cfDNA. Overall, liquid biopsies of cfDNA to monitor IG rearrangements have the potential to provide important diagnostic, prognostic, and predictive information in patients with MM. Full article
(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)
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